Initial investigation of mortality rates and prognostic indicators in horses with colic in Israel: a retrospective study.

REASONS FOR PERFORMING STUDY: Initial assessment of the mortality rates and prognostic indicators in horses with colic presented to a referral hospital in Israel. OBJECTIVES: To determine mortality rates and to identify potential prognostic indicators in horses undergoing treatment for colic. METHODS: The medical records of 208 colic cases were reviewed and mortality rates calculated including 95% confidence intervals. Mortality rates in surgical cases were calculated separately for strangulating and nonstrangulating lesions as well as for lesions of the large and small intestines. Potential prognostic indicators were identified and evaluated by Student's t test or chi2 test, where appropriate. Those found to be significant (P < 0.05) were evaluated in 2 logistic regression models; one including all horses with colic and one for surgical cases only. RESULTS: The overall mortality rate was 51/208 (25%); 5/72 (7%) in medically treated cases, 46/136 (34%) in surgical cases, 30/50 (60%) in strangulating lesions and 15/85 (18%) in nonstrangulating lesions, 17/27 (63%) in cases involving small intestinal lesions and 28/108 (26%) in cases with large intestinal lesions. Clinical parameters found to be significantly associated with death by univariate analysis were medical/surgical treatment, location of lesion, severity of lesion, mucous membrane colour (MM), capillary refill time (CRT) and heart rate. Using a multivariate logistic regression model, including all cases, medical/surgical treatment, CRT and MM were found to be prognostic indicators and when using the surgical cases alone, only CRT and lesion severity remained related to mortality. CONCLUSIONS: Mortality rates were similar or better than those previously reported in most cases, however, studies from the USA and the UK published better success rates for small intestinal surgeries. Cultural attitudes toward euthanasia may be associated with mortality rates. POTENTIAL RELEVANCE: These results assist clinicians in providing an immediate prognosis based on clinical findings at presentation and contribute to an international database that may aid future research in improving treatment of colic.

Pharmacology and inotropic potential of forskolin in the human heart.

We evaluated the effects of the diterpene compound forskolin in human myocardial adenylate cyclase preparations, isolated trabeculae and papillary muscles derived from failing human hearts, and acutely instrumented dogs. Forskolin was a potent, powerful activator of human myocardial adenylate cyclase and produced maximal effects that were 4.82 (normally functioning left ventricle) and 6.13 (failing left ventricle) fold greater than isoproterenol. In contrast to isoproterenol, forskolin retained full activity in membrane preparations derived from failing hearts. In cyclase preparations, forskolin demonstrated unique substrate and Mg2+ kinetic properties that could be distinguished from hormone receptor-coupled agonists or fluoride ion. The adenylate cyclase stimulatory effect of forskolin was synergistic with isoproterenol, apparently due to the location of forskolin activation being beyond the level of hormone receptor-agonist in the receptor-cyclase complex. Forskolin was a potent positive inotrope in failing human myocardium, producing a stimulation of contraction that was similar to isoproterenol. Finally, in open chest dogs forskolin was a positive inotropic agent that reduced preload and afterload. We conclude that forskolin belongs to a class of agents that may have therapeutic potential in the treatment of congestive heart failure.

Prevention of cardiovascular events in variant angina by long-term diltiazem therapy.

In 43 patients with variant angina, the cardiovascular event rate during diltiazem therapy was compared with that in an equal time period before initiation of therapy. Cardiovascular events, that is, myocardial infarction, sudden death and hospitalization for prolonged angina, were decreased significantly (p less than 0.01) during the initial 6 months and mean 19.6 months of therapy. Based on the binomial principle, there were 22 events during the mean 19.6 months before therapy and 2 events during the equal time period on therapy. No patient died during follow-up. The frequency of angina was decreased by 94%. Diltiazem was well tolerated by all patients and no patient had to discontinue therapy because of adverse effects. It is concluded that long-term diltiazem therapy reduces cardiovascular events in patients with variant angina.

High speed rotational coronary atherectomy for patients with diffuse coronary artery disease.

High speed rotational coronary atherectomy was undertaken using the Rotablator in 42 patients who were suboptimal candidates for balloon angioplasty. Most patients (71%) had diffuse coronary artery disease, defined as a stenosis greater than 1 cm in length. Previous restenosis after balloon angioplasty was present in 21% and 10% had an ostial lesion. Adjunctive balloon angioplasty was not used to reduce residual stenosis after atherectomy. The procedure was successful in 76% of patients. Procedural success was achieved in 92% of patients with a lesion less than or equal to 1 cm in length, but in only 70% of patients with a lesion greater than 1 cm in length (p less than 0.01). One patient sustained abrupt closure of the target vessel, resulting in emergency bypass surgery and death. Small non-Q wave myocardial infarction occurred in eight patients (19%) and was associated with a longer lesion. The mean peak creatine kinase value in patients with non-Q wave myocardial infarction was 683 U/liter. Transient regional wall motion abnormalities were noted on the postatherectomy left ventricular angiogram in four of the eight patients with non-Q wave myocardial infarction. Follow-up angiography (at a mean interval of 6.2 +/- 2.6 months) was performed in 91% of patients and revealed restenosis (greater than 50% narrowing) in 59% The resistance rate was 22% for short lesions (less than or equal to 1 cm) and 75% for long lesions (greater than 1 cm) (p less than 0.05). In this study, the results of high speed rotational coronary atherectomy were strongly influenced by lesion length.(ABSTRACT TRUNCATED AT 250 WORDS)

Spontaneous phasic activity of isolated human coronary arteries.

The functional behaviour and pharmacological responses of ring segments of large coronary arteries removed from five patients undergoing cardiac transplantation were studied in vitro. All segments showed spontaneous rhythmic contractions which were markedly dependent on external calcium and were rapidly abolished in calcium-free solutions and by verapamil. The contractions were inhibited by cooling and by anoxia. Phasic activity was enhanced by increasing the external potassium concentration over the range 5 to 20 mmol.litre-1 but was abolished by 120 mmol.litre-1 potassium. Noradrenaline and ergonovine enhanced or induced phasic activity. The behaviour of human coronary arteries resembles that of the portal-mesenteric veins of many species and our results suggest that the activation mechanisms of these two tissues may be similar.

Carbon monoxide encephalopathy: need for appropriate treatment.

The authors describe severe psychiatric and neurological sequelae in a patient who suffered carbon monoxide poisoning as a result of a suicide attempt. A review of the literature revealed that 15 to 40% of survivors of carbon monoxide poisoning develop neuropsychiatric symptoms, often following a period of apparent recovery. The authors advocate an aggressive treatment approach to carbon monoxide poisoning, emphasize the diagnostic value of extensive laboratory testing, and suggest that 2 to 4 weeks of bedrest may prevent delayed neuropsychiatric sequelae.

Platelet monoamine oxidase in chronic schizophrenic patients.

The authors investigated platelet monoamine (MAO) activity in 40 chronic schizophrenic patients, 55 normal control subjects, and 16 hospitalized control subjects. The mean platelet MAO activity for the chronic schizophrenic patients was significantly lower than the mean in either control group. There were no significant differences between the mean platelet MAO activities in 21 chronic paranoid schizophrenic patients compared with 18 chronic undifferentiated schizophrenic patients.

The isolated human epicardial coronary artery.

Ring segments from coronary arteries from recipient hearts of patients receiving cardiac transplants were prepared and mounted in an organ bath. Spontaneous contractile activity, factors that affect basal tone, agonist-induced contractile responses, regional receptor distribution, activity of cardioactive drugs, and species differences were studied. Agents that mediate contraction include histamine, acetylcholine, norepinephrine, potassium and some prostaglandins. Calcium-entry blockers, nitrates and beta-adrenergic agonists caused relaxation. Major species differences exist in coronary vascular pharmacology. Ring segments from human epicardial coronary arteries are suitable for pharmacologic studies, and because of species differences, they offer an ideal model for investigating the pharmacology of the human coronary circulation.

Beta 2 receptors on myocardial cells in human ventricular myocardium.

Beta 2-adrenergic receptors comprise 40% of the total beta-receptor population in failing human right ventricles, as deduced from computer modeling of iodine-125 iodocyanopindolol-ICI 118,551 competition curves. A myocardial cell origin of at least some of the beta 2 subpopulation was demonstrated by documenting a beta 2-receptor mediated positive inotropic response to the selective beta 2 agonist zinterol. It is concluded that beta 2-adrenergic receptors are present on human ventricular myocardial cells.

Efficacy of diltiazem for control of symptoms of coronary arterial spasm.

To evaluate the efficacy of the calcium antagonist diltiazem for therapy of active coronary arterial spasm, 13 patients with clinical variant angina attributed to documented coronary arterial spasm completed a prospective randomized double-blind crossover trial of diltiazem (120 and 240 mg/day) versus placebo. Response was assessed with the diary technique measuring frequency of angina, consumption of nitroglycerin and percent of pain-free days. When 120 mg of diltiazem/day was compared with the paired placebo period there was a significant increase in percent of pain-free days (from 43 to 71 percent [p = 0.03]), but no significant decrease in frequency of angina (p = 0.06) or consumption of nitroglycerin (p = 0.32). When 240 mg of diltiazem/day was compared with the paired placebo period there was a significant increase in percent of pain-free days (from 50 to 79 percent [p = 0.03]) and a significant decrease in both frequency of angina (from 1.6 to 0.4 episodes/day [p = 0.03]) and consumption of nitroglycerin (from 1.3 to 0.4/day [p = 0.01]). Diltiazem was found to be a highly effective drug for control of symptoms of active coronary arterial spasm, without side effects and with excellent patient tolerance.

Diltiazem for long-term therapy of coronary arterial spasm.

The first 36 patients with coronary arterial spasm treated with diltiazem and followed up at the Stanford University Coronary Artery Spasm Clinic for 6 months or longer are described. There were 13 men and 23 women with a mean age of 50.2 years; the mean duration of angina was 36.1 months. All patients had angina at rest with a good or fail response to sublingual nitroglycerin. During a mean of 17.5 months of diltiazem therapy, the frequency of angina was reduced from a mean of 21.5 to 1.3 attacks/week. This 94 percent reduction in pain frequency occurred when either 240 or 360 mg of diltiazem was administered daily. Sixteen patients required the addition of isosorbide dinitrate to achieve a painfree state. Pain breakthrough occurred a mean of 1.7 times during the 17.5 month follow-up period but tended to be of short duration. Six patients had trace to 1+ pedal edema and no other adverse effects occurred. It is concluded that diltiazem is highly effective and well tolerated for the long-term prophylaxis and treatment of angina in patients with coronary spasm.

Selective absorption of ultraviolet laser energy by human atherosclerotic plaque treated with tetracycline.

Tetracycline is an antibiotic that absorbs ultraviolet light at 355 nm and preferentially binds to atherosclerotic plaque both in vitro and in vivo. Tetracycline-treated human cadaveric aorta was compared with untreated aorta using several techniques: absorptive spectrophotometry, which demonstrated a distinct absorptive peak at 355 nm in tetracycline-treated plaque that was absent in treated normal vessel; ultraviolet microscopy, which showed that treated atheroma acquired the characteristic fluorescence of tetracycline under ultraviolet light; and tissue uptake of radiolabeled tetracycline, which showed 4-fold greater uptake by atheroma than by normal vessel. In addition, intravenous tetracycline administered to patients undergoing vascular surgery demonstrated characteristic fluorescence in surgically excised diseased arteries. Because of tetracycline's unique properties, we exposed tetracycline-treated and untreated aorta to ultraviolet laser radiation at a wavelength of 355 nm. We found enhanced ablation of tetracycline-treated atheroma compared with untreated atheroma. The plaque ablation caused by ultraviolet laser radiation was twice as extensive in tetracycline-treated vs nontreated plaque (2.2 +/- 0.25 mm vs 1.3 +/- 0.55 mm, p less than 0.017). This study demonstrates the potential of tetracycline plaque enhancement for the selective destruction of atheroma by ultraviolet laser radiation.

Effects of acetylcholine on epicardial coronary arteries after cardiac transplantation without angiographic evidence of fixed graft narrowing.

The coronary response to acetylcholine was evaluated in 10 patients who had had cardiac transplantation 1 to 8 years earlier and in 4 patients who did not undergo transplantation. All 14 patients had no angiographic evidence of fixed coronary arterial narrowing. Acetylcholine was infused in 10-fold increasing concentrations (10(-6) to 10(-2) M) into the midpoint of the left anterior descending coronary artery by an infusion catheter. Administration was terminated when either vasoconstriction was noted at fluoroscopy or when the maximal acetylcholine concentration was reached. Vascular responses were evaluated by quantitative angiography. All 14 patients had a decrease in coronary lumen size in response to acetylcholine. The mean percentage of vasoconstriction was 37 +/- 24% (p less than 0.001). Combined infusion of nifedipine and the maximal vasoconstricting dose of acetylcholine did not result in a significant reversal of coronary vasoconstriction in all 10 cardiac transplantation patients. It was concluded that acetylcholine is a potent coronary vasoconstrictor in patients who had cardiac transplantation and possibly lacks vasodilating effects in most normal patients without angiographic evidence of coronary artery disease, thus suggesting that acetylcholine might not be a suitable pharmacologic agent for testing endothelial cell integrity.

Tissue response selectivity of calcium antagonists is not due to heterogeneity of [3H]-nitrendipine binding sites.

[3H]-nitrendipine binding data and isolated tissue response for five calcium antagonists were evaluated in rabbit myocardium and aorta. The [3H]-nitrendipine binding site was qualitatively identical in myocardium and aorta, as the [3H]-nitrendipine KD, KIS for nicardipine and nifedipine and interactions with verapamil, D600 and diltiazem were not different in aortic and cardiac membranes prepared by similar means. In contrast, the inhibition of the Ca2+-induced contractile response in right ventricular myocardium and aortic ring segments indicated a greater than 10,000 fold selectivity of nicardipine for antagonism of vascular responses. This resulted in a different order of potency for calcium antagonist interaction with the [3H]-nitrendipine binding site in cardiac membranes (nicardipine greater than nifedipine greater than D600 greater than verapamil greater than diltiazem) as compared to antagonism of myocardial tissue response (D600 greater than verapamil greater than or equal to nifedipine greater than nicardipine greater than or equal to diltiazem). In heart the difference between the potency of nicardipine in binding experiments and tissue response approached 4 orders of magnitude. We conclude that tissue response selectivity of calcium antagonists is not explained by heterogeneity of [3H]-nitrendipine binding sites.

Desensitization to nitroglycerin in vascular smooth muscle from rat and human.

Guanylate cyclase in high speed supernatant fractions obtained from rat thoracic aorta or human coronary arteries pretreated with nitroglycerin exhibited a marked desensitization to activation by nitroglycerin, nitroprusside, and nitric oxide. However, activation of soluble guanylate cyclase by arachidonic acid was unaffected by pretreatment of vessels with nitroglycerin. Furthermore, activation of soluble guanylate cyclase by protoporphyrin IX was increased 4-fold when vessels were pretreated with nitroglycerin. Soluble guanylate cyclase partially purified from nitroglycerin-pretreated rat thoracic aorta by immunoprecipitation with a specific monoclonal antibody exhibited persistent desensitization to nitrate-induced activation. These data suggest that nitroglycerin-induced desensitization of guanylate cyclase to activation by nitrovasodilators represents a stable alteration of the enzyme. In contrast, activation by protoporphyrin IX of guanylate cyclase immunoprecipitated from nitroglycerin-pretreated or control vessels was not significantly different. This suggests that the mechanism of protoporphyrin activation of guanylate cyclase is different than the mechanism with nitrovasodilators. Activation of particulate guanylate cyclase by Lubrol-PX, hemin, or atrial natriuretic factor was not significantly different with enzyme prepared from nitroglycerin-pretreated or control vessels from rat and human. Thus, nitroglycerin-induced desensitization of rat thoracic aorta or human coronary artery results in a relatively stable molecular alteration of soluble guanylate cyclase such that the enzyme is specifically less sensitive to activation by nitrovasodilators whereas the effects of other activators of the enzyme are either unchanged or increased.

Intracytoplasmic eosinophilic hyaline globules in cartilaginous neoplasms: a surgical, pathological, ultrastructural, and electron probe x-ray microanalytic study.

Hyaline globules (HGs), spherical intracytoplasmic eosinophilic droplets, have been associated with a variety of conditions, including hepatocellular carcinoma, lung adenocarcinoma, and Kaposi's sarcoma, but they have not been described in cartilaginous tumors. In specimens of 60 cartilaginous neoplasms we found that 22 of 33 chondrosarcomas (67%), eight of 16 enchondromas (50%), and three of seven soft tissue chondromas (43%) exhibited HGs. HGs were seen more commonly in low grade chondrosarcoma (70%) and were relatively rare in high grade chondrosarcoma (25%). No HGs were identified in three osteochondromas, one synovial chondromatosis, or 15 normal cartilaginous tissues taken from various sites. Cartilage associated HGs ranged in size from 2 to 20 microns, were diastase resistant and periodic acid-Schiff (PAS) stain positive, demonstrated autofluorescence, and variably stained with Mallory's phosphotungstic acid-hematoxylin stain (PTAH). A panel of immunostains did not show any specific staining reactions with HGs. Ultrastructurally the HGs were spherical, non-membrane-bound bodies having complex architectural features associated with profiles of rough endoplasmic reticulum. Electron probe x-ray microanalytic (EPXMA) study showed significant peaks of sulphur and calcium. We conclude that HGs represent secretory products of probable glycoprotein nature, may accumulate in a variety of cartilaginous neoplasms, and may be seen more frequently in low grade chondrosarcomas.

Augmentation ventriculoplasty for treatment of hypertrophic cardiomyopathy.

Augmentation ventriculoplasty has the theoretical potential of partially altering abnormal diastolic properties by enlarging the left ventricular cavity and increasing the end-diastolic volume. This procedure was employed in a 26-year-old woman with symptomatic hypertrophic cardiomyopathy. Postoperatively, she had increased cardiac output and an improvement in clinical symptoms. We conclude that this procedure may be useful in patients with hypertrophic cardiomyopathy who have not responded to traditional medical and surgical therapy.

Studies with isolated human coronary arteries. Some general observations, potential mediators of spasm, role of calcium antagonists.

We studied the basic mechanisms involved in human coronary artery smooth-muscle contraction in an attempt to gain insight into the pathophysiology and pathopharmacology of coronary spasm. coronary arteries were obtained from recipient hearts of patients receiving cardiac transplantation at Stanford University. Coronary ring segments were studied in an organ bath using standard Tyrode's solution. Observation included characterizations of spontaneous contractile activity, factors affecting basal tone, type of agonist-induced contractile respnse, receptor distribution, activity of cardioactive drugs, and species differences. Agents mediating contraction included histamine, acetylcholine, norepinephrine, potassium, and prostaglandins. Because of recent clinical interest in calcium antagonists, diltiazem was studied extensively. Diltiazem demonstrated noncompetitive antagonism to the effects of several agonists and competitive antagonism to calcium. The exact cause and mechanism of coronary spasm is still unknown, but we have identified new areas for future investigation.

Medical therapy of Prinzmetal's variant angina.

Medical therapy for Prinzmetal's variant angina has been treatment of the acute attack with sublingual nitroglycerin. Prophylactic therapy has been more difficult, utilizing long-acting vasodilators that are limited because of their short half-life and side effects when therapeutic doses are used. Alpha-adrenergic blockade has been effective in some patients but is frequently associated with intolerable side effects or apparent development of tolerance to the drug. Preliminary experience from a randomized double-blind trial of diltiazem, a new calcium antagonist, has demonstrated a 90% reduction in pain episodes, with many patients becoming pain-free on the 240-mg daily dose. These data and the lack of adverse side effects demonstrate a dramatically effective therapy for patients with coronary artery spasm.

Ultrastructural and functional studies on prolonged myocardial preservation in an experimental heart transplant model.

The effect of ischemia with hypothermic cardioplegic preservation were studied in a heterotopic isograft rat heart transplant model. Hearts with ischemic time periods of 0.5, 4, 8, and 12 hours (n = 5 to 7 transplants per ischemic time period) were analyzed for structural and functional changes 50 days after transplantation. Postoperative recovery was prolonged with increasing duration of preservation times, but all transplants functioned normally 20 minutes and 50 days after transplantation. Function of right ventricular strips from graft and normal hearts were compared in a muscle bath. No differences were observed between baseline or isoproterenol-stimulated myocardium from all grafts or normal hearts. Electron and light microscopy studies of right and left ventricle and ventricular septum samples demonstrated marked fibrosis at 4, 8, and 12 hours of preservation with no differences between the 4, 8 and 12 hour grafts. There were no other differences in other features examined, including necrotic, mitochondrial, I-band, contractility, nuclear, endothelial cell, or intracellular lipid changes. We conclude that (1) except for significant fibrosis, transplants have normal structure and function after 4, 8, and 12 hours of preservation, (2) in assessing the efficacy of hypothermic cardioplegic preservation, chronic structural changes are more sensitive than functional changes, and (3) hypothermic cardioplegic preservation is feasible up to 12 hours but fibrosis may be the ultimate limiting factor in man.